Fig. 2

Multi-omics approaches to attenuating astrocyte-mediated toxicity. Under pre-symptomatic conditions, astrocytes play a supporting role in maintaining normal functioning of neurons and the central nervous system. As reactive oxygen species (ROS), inflammation and protein aggregates begin to accumulate, coupled with decreased ability to clear waste (autophagy), quiescent astrocytes may be activated to become ALS astrocytes which are highly secretive. These astrocyte-derived extracellular vesicles contain harmful proinflammatory cytokines and chemokines which ultimately result in degeneration of motor neurons and dysfunctional motor unit. The use of multi-omics (e.g., genomics, transcriptomics, proteomics, metabolomics) will allow for in-depth understanding of complex and multifactorial diseases such as ALS. Integration of different omics layers is crucial for uncovering changes in ALS astrocytes during disease onset and progression, paving the way for development of new therapeutics which can revert A1-like ALS astrocytes to A2 neuroprotective astrocytes